Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription.
Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription.
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DOI：
10.1016/j.molcel.2014.03.026
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发表时间：
2014-04-10
期刊：
影响因子：
16
通讯作者：
Dean, Caroline
中科院分区：
文献类型：
--
作者：
Marquardt, Sebastian;Raitskin, Oleg;Wu, Zhe;Liu, Fuquan;Sun, Qianwen;Dean, Caroline
反义转录在许多基因组中广泛存在；然而，有多少是功能性的仍存在激烈的争论。我们正在研究一组长的非编码反义转录本的功能，统称为COOLAIR，在拟南芥开花基因座C(FLC)产生。COOLAIR起始于主要正义转录子Poly(A)位点的下游，提前终止或延伸到FLC启动子区域。我们现在证明COOLAIR的剪接在功能上是重要的。这是通过分析核心剪接体成分Prp8的亚型突变而揭示的。Prp8突变扰乱了将COOLAIR处理与FLC基因体组蛋白去甲基化联系起来的共转录反馈机制，并减少了FLC的转录。通过干扰COOLAIR的产生和突变COOLAIR近端剪接受体位点，证实了COOLAIR剪接在这种抑制机制中的重要性。我们的发现表明，一个长的非编码转录本的剪接改变可以通过共转录耦合机制定量调节基因的表达。非编码反义转录物的选择性剪接通过将反义剪接与染色质状态偶联来影响开花拟南芥FLC基因转录，受lncRNA异构体、正反馈链、染色质状态和反义转录物剪接的影响。证明了与拟南芥花抑制基因FLC反义的非编码转录本是交替剪接的。干扰这种选择性剪接会在数量上改变FLC的转录，并影响开花的时间。因此，这项工作揭示了拟南芥中一个长的非编码反义转录本的功能。
Antisense transcription is widespread in many genomes; however, how much is functional is hotly debated. We are investigating functionality of a set of long noncoding antisense transcripts, collectively called COOLAIR, produced at Arabidopsis FLOWERING LOCUS C (FLC). COOLAIR initiates just downstream of the major sense transcript poly(A) site and terminates either early or extends into the FLC promoter region. We now show that splicing of COOLAIR is functionally important. This was revealed through analysis of a hypomorphic mutation in the core spliceosome component PRP8. The prp8 mutation perturbs a cotranscriptional feedback mechanism linking COOLAIR processing to FLC gene body histone demethylation and reduced FLC transcription. The importance of COOLAIR splicing in this repression mechanism was confirmed by disrupting COOLAIR production and mutating the COOLAIR proximal splice acceptor site. Our findings suggest that altered splicing of a long noncoding transcript can quantitatively modulate gene expression through cotranscriptional coupling mechanisms. Alternative splicing of noncoding antisense transcripts affects flowering Arabidopsis FLC gene transcription modulated by lncRNA isoforms Positive feedback links chromatin state and antisense transcript splicing Quantitative gene regulation by coupling antisense splicing to chromatin states Marquardt et al. demonstrate that noncoding transcripts antisense to the Arabidopsis floral repressor gene FLC are alternatively spliced. Interfering with this alternative splicing alters FLC transcription quantitatively and affects the timing of flowering. Thus, this work reveals a function for a long noncoding antisense transcript in Arabidopsis.
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